血液系统恶性肿瘤治疗中的血液毒性问题

I. Kriachok
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The main causes of thrombocytopenia in cancer patients are chemotherapy (ChT) and radiation therapy (RT), however, the diagnosis should take into account all possible nosological options. The assessment should be performed if the platelet count is <100,000/μl. The normal lifespan of platelets is 8-10 days, so after many types of ChT thrombocytopenia develops about 7th days after treatment, reaches a maximum of 14th days and ends in 28-35th days. After RT thrombocytopenia usually starts in 7-10th days after its termination and is present during 30-60 days. Before treating thrombocytopenia, the need for ChT should be re-evaluated and the risk of bleeding assessed, and the ChT regimen should be changed if possible. If the risk of bleeding is high or the platelet count is critically low, platelet transfusion is prescribed, however, it has recently been found that absolute platelet count is not a predictor of bleeding risk in this patient population (PLADO study). In addition, platelet transfusion is limited in resources and costly, and is accompanied by the risk of side effects (acute lung damage due to transfusion, fever, bacterial sepsis, development of transfusion intolerance). This became the basis for the search for alternative treatment options. Recombinant interleukin-11 (oprelvekin) reduces the need for platelet transfusion from 96 to 70 % of patients on ChT. However, although this drug is FDA-approved, it is characterized by a large number of side effects. In turn, thrombopoietin receptor agonists (subcutaneous romiplostin, oral eltrombopag) bind to the corresponding receptors and increase the number of platelets in the blood. The effectiveness of treatment is within 70 %. Emaplag (“Yuria-Pharm”) is the first and only eltrombopag in Ukraine. Emaplag is indicated for the treatment of thrombocytopenia caused by ChT in patients with solid tumors, patients with platelet counts <50×109/L, and in cases where the physician decides to increase platelet count. With regard to anemias, their main causes in cancer patients are the factors of the underlying disease (bone marrow infiltration, infectious processes), the impact of ChT or RT, other causes (malnutrition, bleeding, renal dysfunction). Examination of patients with anemia should include history taking, evaluation of blood smear and iron metabolism, exclusion of occult gastrointestinal bleeding and renal failure, Coombs’ test, determination of endogenous erythropoietin. Treatment options for ChT-induced anemia include blood transfusions and the use of erythropoietins (epoetins α and β, darbepoetin) with or without iron supplements (oral or intravenous). The advantages of using erythropoietin include reducing the need for transfusion of erythrocyte mass, a gradual increase in hemoglobin, increasing quality of life. However, erythropoietins are not recommended for use in cancer patients who do not receive ChT or receive RT, because in these cases, their use is associated with an increased mortality risk. Because in some patient groups erythropoietins accelerate tumor growth or reduce survival, the patient must give a written informed consent for their use. Given these data, it is advisable to prescribe intravenous iron, as it allows not only to quickly increase hemoglobin and improve quality of life, but also to reduce the dosage of erythropoietins. Iron carboxymaltose if the most modern parenteral iron preparation. It is characterized by low toxicity and high stability. \nConclusions. 1. Thromboconcentrate transfusion is a fast and effective way to correct thrombocytopenia, which has a number of disadvantages. 2. Thrombopoietin receptor agonists (eltrombopag) make it possible to increase the effectiveness of treatment without interrupting the planned therapy. 3. In the presence of anemia, all possible causes should be corrected before prescribing erythropoietins. 4. If the anemia is caused by ChT, the patient needs to take erythropoietins. 5. Addition of intravenous iron preparations to erythropoietin therapy significantly increases the effectiveness of treatment.","PeriodicalId":13681,"journal":{"name":"Infusion & Chemotherapy","volume":"15 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2020-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Problems of hematological toxicity during the treatment of blood system malignancies\",\"authors\":\"I. Kriachok\",\"doi\":\"10.32902/2663-0338-2020-3.2-156-158\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background. Treatment of blood malignancies is often accompanied by the hematological toxicity. Thrombocytopenia is one of the most common phenomena, which can be caused by pseudothrombocytopenia, production deficiency or increased destruction of platelets, their pathological distribution or aggregation. \\nObjective. To determine the features of hematological toxicity in the treatment of malignant blood diseases. \\nMaterials and methods. Analysis of literature data and recommendations on this topic. \\nResults and discussion. Diagnosis of thrombocytopenia involves a detailed study of a peripheral blood smear to assess the morphology of all cells, as well as additional studies (determination of lactate dehydrogenase, D-dimer, fibrinogen, etc.; aspiration and bone marrow biopsy; virological and bacteriological studies; clinical examination). The main causes of thrombocytopenia in cancer patients are chemotherapy (ChT) and radiation therapy (RT), however, the diagnosis should take into account all possible nosological options. The assessment should be performed if the platelet count is <100,000/μl. The normal lifespan of platelets is 8-10 days, so after many types of ChT thrombocytopenia develops about 7th days after treatment, reaches a maximum of 14th days and ends in 28-35th days. After RT thrombocytopenia usually starts in 7-10th days after its termination and is present during 30-60 days. Before treating thrombocytopenia, the need for ChT should be re-evaluated and the risk of bleeding assessed, and the ChT regimen should be changed if possible. If the risk of bleeding is high or the platelet count is critically low, platelet transfusion is prescribed, however, it has recently been found that absolute platelet count is not a predictor of bleeding risk in this patient population (PLADO study). In addition, platelet transfusion is limited in resources and costly, and is accompanied by the risk of side effects (acute lung damage due to transfusion, fever, bacterial sepsis, development of transfusion intolerance). This became the basis for the search for alternative treatment options. Recombinant interleukin-11 (oprelvekin) reduces the need for platelet transfusion from 96 to 70 % of patients on ChT. However, although this drug is FDA-approved, it is characterized by a large number of side effects. In turn, thrombopoietin receptor agonists (subcutaneous romiplostin, oral eltrombopag) bind to the corresponding receptors and increase the number of platelets in the blood. The effectiveness of treatment is within 70 %. Emaplag (“Yuria-Pharm”) is the first and only eltrombopag in Ukraine. 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引用次数: 0

摘要

背景。血液恶性肿瘤的治疗常伴有血液毒性。血小板减少症是最常见的现象之一,它可以由假性血小板减少症、血小板生产不足或血小板破坏增加、血小板病理分布或聚集引起。目标。目的:探讨恶性血液病治疗的血液学毒性特点。材料和方法。本课题的文献资料分析及建议。结果和讨论。血小板减少症的诊断包括对外周血涂片的详细研究,以评估所有细胞的形态,以及额外的研究(乳酸脱氢酶、d -二聚体、纤维蛋白原等的测定;穿刺和骨髓活检;病毒学和细菌学研究;临床检查)。癌症患者血小板减少的主要原因是化疗(ChT)和放疗(RT),然而,诊断应考虑到所有可能的分类学选择。血小板计数<10万/μl时应进行评估。血小板的正常寿命为8-10天,因此在多种类型的ChT后,血小板减少在治疗后约7天开始,最多可达14天,并在28-35天结束。RT后血小板减少症通常在终止后7-10天开始,并在30-60天出现。在治疗血小板减少症之前,应重新评估ChT的需要和出血风险,如果可能的话,应改变ChT治疗方案。如果出血风险高或血小板计数极低,则规定输注血小板,然而,最近发现绝对血小板计数并不是该患者人群出血风险的预测因子(PLADO研究)。此外,血小板输注资源有限,费用昂贵,并伴有副作用的风险(输血引起的急性肺损伤、发热、细菌性败血症、输血不耐受的发生)。这成为了寻找替代治疗方案的基础。重组白细胞介素-11 (oprelvekin)使接受ChT治疗的患者的血小板输注需求从96%减少到70%。然而,虽然这种药物是fda批准的,但它的特点是副作用很多。反过来,血小板生成素受体激动剂(皮下romiplostin,口服eltrombopag)与相应的受体结合,增加血液中血小板的数量。治疗的有效性在70%以内。Emaplag(“Yuria-Pharm”)是乌克兰第一个也是唯一一个电子药物。Emaplag适用于治疗实体瘤患者、血小板计数<50×109/L的患者以及医生决定增加血小板计数的患者中由ChT引起的血小板减少症。至于癌症患者的贫血,其主要原因是潜在疾病的因素(骨髓浸润、感染过程)、ChT或RT的影响、其他原因(营养不良、出血、肾功能障碍)。贫血患者的检查应包括病史、血涂片及铁代谢评价、排除隐匿性胃肠道出血及肾功能衰竭、库姆斯试验、测定内源性促红细胞生成素。治疗方案包括输血和使用促红细胞生成素(epoetins α和β, darbepoetin)加或不加铁补充剂(口服或静脉注射)。使用促红细胞生成素的优点包括减少红细胞输注的需要,逐渐增加血红蛋白,提高生活质量。然而,促红细胞生成素不推荐用于未接受ChT或RT治疗的癌症患者,因为在这些情况下,促红细胞生成素的使用与死亡风险增加有关。由于在某些患者群体中,促红细胞生成素会加速肿瘤生长或降低生存率,因此患者使用促红细胞生成素必须给予书面知情同意。鉴于这些数据,建议静脉注射铁,因为它不仅可以迅速增加血红蛋白和改善生活质量,而且还可以减少促红细胞生成素的剂量。羧麦芽糖铁是最现代的肠外铁制剂。具有低毒性、高稳定性的特点。结论:1。血栓浓缩输血是纠正血小板减少症的一种快速有效的方法,但它有许多缺点。2. 血小板生成素受体激动剂(eltrombopag)可以在不中断计划治疗的情况下增加治疗的有效性。3.在出现贫血的情况下,在开促红细胞生成素处方之前,应纠正所有可能的原因。4. 如果贫血是由ChT引起的,患者需要服用促红细胞生成素。5. 在促红细胞生成素治疗中加入静脉铁制剂可显著提高治疗效果。
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Problems of hematological toxicity during the treatment of blood system malignancies
Background. Treatment of blood malignancies is often accompanied by the hematological toxicity. Thrombocytopenia is one of the most common phenomena, which can be caused by pseudothrombocytopenia, production deficiency or increased destruction of platelets, their pathological distribution or aggregation. Objective. To determine the features of hematological toxicity in the treatment of malignant blood diseases. Materials and methods. Analysis of literature data and recommendations on this topic. Results and discussion. Diagnosis of thrombocytopenia involves a detailed study of a peripheral blood smear to assess the morphology of all cells, as well as additional studies (determination of lactate dehydrogenase, D-dimer, fibrinogen, etc.; aspiration and bone marrow biopsy; virological and bacteriological studies; clinical examination). The main causes of thrombocytopenia in cancer patients are chemotherapy (ChT) and radiation therapy (RT), however, the diagnosis should take into account all possible nosological options. The assessment should be performed if the platelet count is <100,000/μl. The normal lifespan of platelets is 8-10 days, so after many types of ChT thrombocytopenia develops about 7th days after treatment, reaches a maximum of 14th days and ends in 28-35th days. After RT thrombocytopenia usually starts in 7-10th days after its termination and is present during 30-60 days. Before treating thrombocytopenia, the need for ChT should be re-evaluated and the risk of bleeding assessed, and the ChT regimen should be changed if possible. If the risk of bleeding is high or the platelet count is critically low, platelet transfusion is prescribed, however, it has recently been found that absolute platelet count is not a predictor of bleeding risk in this patient population (PLADO study). In addition, platelet transfusion is limited in resources and costly, and is accompanied by the risk of side effects (acute lung damage due to transfusion, fever, bacterial sepsis, development of transfusion intolerance). This became the basis for the search for alternative treatment options. Recombinant interleukin-11 (oprelvekin) reduces the need for platelet transfusion from 96 to 70 % of patients on ChT. However, although this drug is FDA-approved, it is characterized by a large number of side effects. In turn, thrombopoietin receptor agonists (subcutaneous romiplostin, oral eltrombopag) bind to the corresponding receptors and increase the number of platelets in the blood. The effectiveness of treatment is within 70 %. Emaplag (“Yuria-Pharm”) is the first and only eltrombopag in Ukraine. Emaplag is indicated for the treatment of thrombocytopenia caused by ChT in patients with solid tumors, patients with platelet counts <50×109/L, and in cases where the physician decides to increase platelet count. With regard to anemias, their main causes in cancer patients are the factors of the underlying disease (bone marrow infiltration, infectious processes), the impact of ChT or RT, other causes (malnutrition, bleeding, renal dysfunction). Examination of patients with anemia should include history taking, evaluation of blood smear and iron metabolism, exclusion of occult gastrointestinal bleeding and renal failure, Coombs’ test, determination of endogenous erythropoietin. Treatment options for ChT-induced anemia include blood transfusions and the use of erythropoietins (epoetins α and β, darbepoetin) with or without iron supplements (oral or intravenous). The advantages of using erythropoietin include reducing the need for transfusion of erythrocyte mass, a gradual increase in hemoglobin, increasing quality of life. However, erythropoietins are not recommended for use in cancer patients who do not receive ChT or receive RT, because in these cases, their use is associated with an increased mortality risk. Because in some patient groups erythropoietins accelerate tumor growth or reduce survival, the patient must give a written informed consent for their use. Given these data, it is advisable to prescribe intravenous iron, as it allows not only to quickly increase hemoglobin and improve quality of life, but also to reduce the dosage of erythropoietins. Iron carboxymaltose if the most modern parenteral iron preparation. It is characterized by low toxicity and high stability. Conclusions. 1. Thromboconcentrate transfusion is a fast and effective way to correct thrombocytopenia, which has a number of disadvantages. 2. Thrombopoietin receptor agonists (eltrombopag) make it possible to increase the effectiveness of treatment without interrupting the planned therapy. 3. In the presence of anemia, all possible causes should be corrected before prescribing erythropoietins. 4. If the anemia is caused by ChT, the patient needs to take erythropoietins. 5. Addition of intravenous iron preparations to erythropoietin therapy significantly increases the effectiveness of treatment.
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